Polynucleotide sequences containing as few as one covalently-bound mercury atom per two hundred bases are selectively and quantitatively retained when chromatographed on columns of sulfhydryl-agarose. Products adsorbed to the resin are readily recovered for further analysis by eluting with buffers containing mercaptoethanol. This affinity-chromatography system provides a simple and highly efficient procedure for isolating selected polynucleotide sequence. We propose to purify and analyze specific subsets of mammalian (cellular and viral) DNA by using mercuri-polynucleotides (as hybridization probes), mercuri- oligonucleotides (as polymerase primers) and mercuri-nucleotides (as polymerase substrates), in conjunction with sulfhydryl-agarose chromatography.